Plasma VP8∗-Binding Antibodies in Rotavirus Infection and Oral Vaccination in Young Bangladeshi Children

Benjamin Lee; E Ross Colgate; Marya Carmolli; Dorothy M Dickson; Soyeon Gullickson; Sean A Diehl; Rifat Ara; Masud Alam; Golam Kibria; Md Abdul Kader; Sajia Afreen; Tahsin Ferdous; Rashidul Haque; Beth D Kirkpatrick

doi:10.1093/jpids/piab120

Plasma VP8∗-Binding Antibodies in Rotavirus Infection and Oral Vaccination in Young Bangladeshi Children

J Pediatric Infect Dis Soc. 2022 Apr 30;11(4):127-133. doi: 10.1093/jpids/piab120.

Authors

Benjamin Lee^{1

2}, E Ross Colgate^{2

3}, Marya Carmolli^{2

3}, Dorothy M Dickson^{2

3}, Soyeon Gullickson^{2

3}, Sean A Diehl^{2

3}, Rifat Ara⁴, Masud Alam⁴, Golam Kibria⁴, Md Abdul Kader⁴, Sajia Afreen⁴, Tahsin Ferdous⁴, Rashidul Haque⁴, Beth D Kirkpatrick^{2

3}

Affiliations

¹ Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.
² Translational Global Infectious Diseases Research Center, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.
³ Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.
⁴ Department of Parasitology and Emerging Infections, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.

Abstract

Background: Despite the availability and success of live-attenuated oral vaccines, rotavirus (RV) remains the leading cause of pediatric gastroenteritis worldwide. Next-generation vaccines targeting RV VP8∗ are under evaluation, but the role of VP8∗-specific antibodies in human immunity to RV and their potential as immune correlates of protection remains underexplored.

Methods: We measured plasma RV VP8∗-binding antibodies in 2 cohorts of young children in Dhaka, Bangladesh. Plasma from a cohort study of 137 unvaccinated children aged 6-24 months old hospitalized with acute gastroenteritis was assessed for VP8∗ antibody seropositivity. VP8∗ antibodies were compared with the current standard for RV immunity, total RV-specific IgA (RV-IgA). Additionally, VP8∗ antibody responses were measured as part of an immunogenicity trial of a monovalent, oral, live-attenuated RV vaccine (Rotarix).

Results: Fewer children with acute RV gastroenteritis were seropositive for VP8∗-binding IgA or IgG antibodies at hospital admission compared with RV-IgA, suggesting that the absence of VP8∗-binding antibodies more accurately predicts susceptibility to RV gastroenteritis than RV-IgA in unvaccinated children. However, when present, these antibodies appeared insufficient to protect fully from disease and no threshold antibody level for protection was apparent. In vaccinated children, these antibodies were very poorly induced by Rotarix vaccine, suggesting that VP8∗-specific antibodies alone are not necessary for clinical protection following oral vaccination.

Conclusions: This work suggests that VP8∗-binding antibodies may not be sufficient or necessary for protection from RV gastroenteritis following prior RV infection or oral vaccination; the role of VP8∗ antibodies induced by parenteral vaccination with non-replicating vaccines remains to be determined.

Keywords: correlates of protection; oral vaccines; rotavirus; rotavirus vaccines; viral gastroenteritis.

MeSH terms

Antibodies, Viral
Bangladesh
Child, Preschool
Cohort Studies
Gastroenteritis* / prevention & control
Humans
Immunoglobulin A
Infant
Rotavirus Infections* / prevention & control
Rotavirus Vaccines*
Rotavirus*
Vaccination
Vaccines, Attenuated

Substances

Antibodies, Viral
Immunoglobulin A
Rotavirus Vaccines
Vaccines, Attenuated

Abstract

MeSH terms

Substances

Grants and funding